Viral Hepatitis

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Human leukocyte antigen class II associations with hepatitis C virus clearance and virus-specific CD4 T cell response among Caucasians and African Americans†

  1. Rebecca A. Harris1,2,3,
  2. Kazushi Sugimoto1,2,
  3. David E. Kaplan1,2,
  4. Fusao Ikeda1,2,
  5. Malek Kamoun4,
  6. Kyong-Mi Chang1,2,‡,*

Article first published online: 7 JUN 2008

DOI: 10.1002/hep.22287

Issue

Hepatology

Hepatology

Volume 48, Issue 1, pages 70–79, July 2008

Additional Information

How to Cite

Harris, R. A., Sugimoto, K., Kaplan, D. E., Ikeda, F., Kamoun, M. and Chang, K.-M. (2008), Human leukocyte antigen class II associations with hepatitis C virus clearance and virus-specific CD4 T cell response among Caucasians and African Americans. Hepatology, 48: 70–79. doi: 10.1002/hep.22287

Author Information

  1. 1

    Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA

  2. 2

    Philadelphia Veterans Affairs Medical Center, Philadelphia, PA

  3. 3

    Haverford College, Haverford, PA

  4. 4

    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA

  1. ‡

    fax: 215-823-4394.

*Division of Gastroenterology, University of Pennsylvania School of Medicine, 600 CRB, 415 Curie Boulevard, Philadelphia, PA 19014

  1. †

    Potential conflict of interest: Nothing to report.

Publication History

  1. Issue published online: 20 JUN 2008
  2. Article first published online: 7 JUN 2008
  3. Manuscript Accepted: 10 FEB 2008
  4. Manuscript Received: 13 OCT 2007

Funded by

  • National Institutes of Health (NIH). Grant Numbers: AI47519, AA12849
  • Philadelphia VA Medical Research
  • NIH/National Institute of Diabetes and Digestive and Kidney Diseases Center of Molecular Studies in Digestive and Liver Diseases P30DK50306 and its Molecular Biology and Cell Culture Core Facilities
  • NIH Public Health Service Research Grant. Grant Number: M01-RR00040
  • University of Pennsylvania Summer Undergraduate Scholars Program
  • Howard Hughes Interdisciplinary Scholar Award at Haverford College

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Abstract

The outcome of hepatitis C virus (HCV) infection has been associated with antiviral CD4 T cell response, human leukocyte antigens (HLA) class II genotypes, and ethnicity. However, HLA class II molecules restrict the nature of CD4 T cell response, and HLA distributions differ between ethnic groups. In this study, we asked whether HLA class II genotypes associated with HCV clearance are shared between Caucasian and African Americans and whether they contribute to enhanced antiviral CD4 T cell response. In a cohort of 93 HCV-seropositive subjects from Northeast America with defined ethnicity, virological outcome, and HCV-specific CD4 T cell proliferation, we confirm the previously reported associations between HCV clearance and two HLA types (DQB1*03, DRB1*11) while identifying a new association with DRB3*02. Strikingly, these associations were identified only among Caucasian [DQB1*03: odds ratio (OR), 10.4; P = 0.031, DRB1*11: OR, 7.0, P = 0.019; DRB3*02: OR, 8.3, P = 0.005; DQB1*03–DRB3*02: OR, 13.5, P = 0.001) but not among African American patients. Furthermore, although HLA DQB1*03, DRB1*11, and DRB3*02 genotypes were associated with increased HCV-specific CD4 T cell response in univariate analyses, these associations were lost when controlling for virological outcomes. Conclusion: We conclude that the immunogenetic basis for HCV clearance differs between ethnic groups and that the association between HLA class II and HCV clearance is not directly explained by antiviral CD4 T cell response. (HEPATOLOGY 2008.)

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